Several different teratogens produce similar craniofacial anomalies in experimental animals and in humans, suggesting that there may be a common pathway involved in the mechanism of teratogenesis by different agents. Based on our own observations and on the work from other laboratories, we have formulated a theory that embryonic development requires normally functioning signal transduction pathway linked to the arachidonic acid cascade via protein kinase C, and that some teratogens produce anomalies by inhibiting this pathway. Dysmorphogenesis by glucocorticoids, lithium, diphenylhydantoin (DPH) and maternal diabetes all appear to involve this pathway: the teratogenic effects of lithium and maternal diabetes have been ascribed to a deficiency of myoinositol, while those of maternal diabetes and DPH have been linked to a deficiency of arachidonic acid. We plan to test this hypothesis by using lithium carbonate and DPH, to see if l)the teratogens produce measurable inhibitions in the embryonic tissue of the key enzymes and products of the putative pathway distal to the inhibition site 2) The teratogens produce changes in the distribution of the key enzymes and products of the pathway histochemically 3)the anomalies can be corrected by reversing the inhibition 4) the teratogens produce inhibition of programmed cell death in the neural tube and in the palate, and interference of transformation/migration of medial edge epithelium of the palate. Mouse embryo culture and mouse in vivo experiments will be used for the experiments.